Acid‐base homeostasis is crucial for normal physiology, metabolism, and functions of living organisms. Thus, the development of effective techniques to monitor it either in vitro or in vivo is in great demand. Herein, a series of multifunctional oxazine‐containing polyheterocycles with aggregation‐induced emission characteristics are in situ generated by metal‐free one‐pot A3 polymerizations of terminal diynes, dialdehydes, and ureas. Most of the polymers are synthesized with high molecular weights (Mw up to 49 900) in nearly quantitative yields and display intense solid‐state emission and remarkable fluorescence response to protonation and deprotonation. Based on the unique photophysical properties, a fast responsive and reversible fluorescent sensor for ammonia with a detection limit of 960 ppb is achieved and applied for detecting biogenic amines and seafood spoilage. Besides, the polymeric nanoparticles show excellent lysosome‐targeting specificity in cell imaging. The polyheterocycles show ratiometric pH sensing behavior with a broad acid‐base response window from pH 1 to 9, which shed light on visualizing physiologic pH in gastrointestinal tract. Taking freshwater Cladocera Moina macrocopa as a model organism, in vivo mapping of its intestinal pH shows an increased pH gradient approximately from 4.2 to 7.8 along the foregut, midgut, and hindgut. Visualization of biogenic amines, food spoilage detection, lysosome‐targeted cell imaging, and in vivo ratiometric mapping of intestinal pH is realized by acid‐base responsive polyheterocycles with intense solid‐state emission, which are synthesized via facile and efficient metal‐free multicomponent polymerizations. In vitro and in vivo monitoring acid‐base homeostasis is now easily accessible in a real‐time, noninvasive, and on‐site manner.